4-(2-bromophenylamino)-1-(phenylmethyl)-4-piperidinecarbonitrile | 240486-11-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: 4-(2-bromophenylamino)-1-(phenylmethyl)-4-piperidinecarbonitrile
• 英文别名: N-benzyl-4-((2-bromophenyl)amino)piperidine-4-carbonitrile；1-benzyl-4-(2-bromoanilino)piperidine-4-carbonitrile
• CAS: 240486-11-7
• 化学式: C₁₉H₂₀BrN₃
• 分子量: 370.292
• InChiKey: ZMRYLAWIURKRAL-UHFFFAOYSA-N

物化性质

• 熔点：
  91-93 °C
• 沸点：
  507.9±50.0 °C(Predicted)
• 密度：
  1.38±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  39.1
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4-(2-bromophenylamino)-1-(phenylmethyl)-4-piperidinecarbonitrile 在 偶氮二异丁腈 、 1-氯乙基氯甲酸酯 、 三正丁基氢锡 、 sodium hexamethyldisilazane 、 potassium carbonate 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 83.67h， 生成 1'-(3,3-diphenylpropyl)-1-(2-propenyl)-spiro[2H-indole-2,4'-piperidin]-3(1H)-one
  参考文献：
  名称：

  Conformational Switching and the Synthesis of Spiro[2H-indol]-3(1H)-ones by Radical Cyclization

  摘要：

  Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4'-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexane-carbonitrile (3, X-R-2 = CH2), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R-2 = CH2). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2e and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.

  DOI：

  10.1021/jo970105t
• 作为产物：
  描述：

  N-苄基哌啶酮 、 三甲基氰硅烷 、 2-溴苯胺 以 溶剂黄146 为溶剂， 反应 65.0h， 以69%的产率得到4-(2-bromophenylamino)-1-(phenylmethyl)-4-piperidinecarbonitrile
  参考文献：
  名称：

  Conformational Switching and the Synthesis of Spiro[2H-indol]-3(1H)-ones by Radical Cyclization

  摘要：

  Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4'-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexane-carbonitrile (3, X-R-2 = CH2), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R-2 = CH2). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2e and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.

  DOI：

  10.1021/jo970105t

文献信息

• [EN] DGK TARGETING COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS DE CIBLAGE DE DGK ET UTILISATIONS ASSOCIÉES
  申请人：[en]ARVINAS OPERATIONS, INC.

  公开号：WO2023150186A1

  公开（公告）日：2023-08-10

  Disclosed herein are compounds of Formula (A), or a pharmaceutically acceptable salt thereof, which inhibit the activity of one or both of diacylglycerol kinase alpha (DGKα). These compounds are useful in the treatment of proliferative diseases (e.g., cancer) and viral infections.
• Discovery and structure-activity relationships of spiroindolines as novel inducers of oligodendrocyte progenitor cell differentiation
  作者：Katsushi Katayama、Yoshikazu Arai、Kenji Murata、Shoichi Saito、Tsutomu Nagata、Kouhei Takashima、Ayako Yoshida、Makoto Masumura、Shuichi Koda、Hiroyuki Okada、Tsuyoshi Muto

  DOI：10.1016/j.bmc.2020.115348

  日期：2020.3

  A novel series of spiroindoline derivatives was discovered for use as inducers of oligodendrocyte progenitor cell (OPC) differentiation, resulting from optimization of screening hit 1. Exploration of structure-activity relationships led to compound 18, which showed improved potency (rOPC EC50 = 0.0032 mu M). Furthermore, oral administration of compound 18 significantly decreased clinical severity in an experimental autoimmune encephalomyelitis (EAE) model.
• Conformational Switching and the Synthesis of Spiro[2<i>H</i>-indol]-3(1<i>H</i>)-ones by Radical Cyclization
  作者：Richard Sulsky、Jack Z. Gougoutas、John DiMarco、Scott A. Biller

  DOI：10.1021/jo970105t

  日期：1999.7.1

  Radical cyclization of 1-(2-bromophenylamino)cyclohexanecarbonitriles (3, X = CH) and 4-(2-bromophenylamino)-4-piperidinecarbonitriles (3, X = N) provide spiro[2H-indole-2-cyclohexan]3(1H)-imines (5, X = CH) and spiro[2H-indole-2,4'-piperidin]-3(1H)-imines (5, X = N), respectively, in 33-57% yields. This contradicts a recent report that 1-(2-bromophenylamino)cyclohexane-carbonitrile (3, X-R-2 = CH2), treated under apparently identical conditions, led only to nitrile transfer product 6 (X-R-2 = CH2). Acidic hydrolyses of the imines provide the corresponding ketones 2 in quantitative yields. Single-crystal X-ray analyses of ketone 2e and nitrile 3e indicate that the relative configuration of the aromatic nitrogen has been inverted during the cyclization. In addition, NOE NMR analyses of spiroindolepiperidine 2e and its aniline-nitrogen-methylated analogue 10a show that the relative conformation of the piperidine ring has inverted. Thus, methylation of 2c acts as a conformational "switch" for the spiroindolepiperidine ring system.